The dynamic epitranscriptome: N6-methyladenosine and gene expression control

Two recent independent studies demonstrated that N6-methyladenosine (m6A) is a widespread base modification in the mammalian transcriptome, which exhibits a unique enrichment near the stop codon and in the untranslated regions (UTRs) of mRNAs.Recent studies have identified methyltransferase-like 3 (METTL3), METTL14 and Wilms tumour 1-associated protein (WTAP) as components of an m6A methyltransferase complex. Further characterization of this complex will be needed to understand the dynamics and specificity of adenosine methylation in various classes of cellular RNA.FTO (fat mass and obesity-associated protein) and ALKBH5 (α-ketoglutarate-dependent dioxygenase alkB homologue 5) are the two m6A demethylating enzymes identified to date. Based on studies of the mRNA targeting specificity and tissue-specific expression patterns of these enzymes, however, it is likely that additional m6A demethylases exist.m6A probably functions by recruiting m6A binding proteins, which influence RNA processing and regulation. Although a small number of m6A-binding proteins have been identified, much work remains to understand the full repertoire of m6A-binding proteins and how they contribute to mRNA regulation.Although m6A probably has many functions, studies so far suggest that it has a role in splicing regulation and mRNA stability.